Low density lipoprotein nanocarriers for targeted delivery of omega-3 polyunsaturated fatty acids to cancer

Abstract

An LDL nanocarrier is an effective and appropriate transporter for DHA in biological systems. The LDL-DHA nanoparticle was shown to be preferentially cytotoxic to malignant liver cells. These LDL-DHA nanoparticles show great promise as an anti-cancer agent. In particular embodiments, the nanoparticles exhibit a diameter of 15 to 30 nm.

What is claimed is: 
     
       1. A composition comprising a lipid nanoparticle comprising a ω-3 polyunsaturated fatty acid and lacking another anti-cancer agent, wherein said lipid nanoparticle is about 15 nm to 30 nm in diameter, wherein said lipid nanoparticle exhibits unaltered polyunsaturated fatty acid, unaltered z-average particle size, unaltered peroxidation, unlatered polydispersity index, unaltered % transmittance and unaltered zeta potential over one month under ambient conditions. 
     
     
       2. A composition comprising a lipid nanoparticle consisting essentially of low density lipoprotein (LDL) and a ω-3 polyunsaturated fatty acid, wherein said lipid nanoparticle is about 15 nm to 30 nm in diameter, wherein said lipid nanoparticle exhibits unaltered polyunsaturated fatty acid, unaltered z-average particle size, unaltered peroxidation, unlatered polydispersity index, unaltered % transmittance and unaltered zeta potential over one month under ambient conditions. 
     
     
       3. A composition comprising a lipid nanoparticle and a therapeutically effective amount of a ω-3 polyunsaturated fatty acid not conjugated to another anti-cancer agent, wherein said lipid nanoparticle is about 15 nm to 30 nm in diameter, wherein said lipid nanoparticle exhibits unaltered polyunsaturated fatty acid, unaltered z-average particle size, unaltered peroxidation, unlatered polydispersity index, unaltered % transmittance and unaltered zeta potential over one month under ambient conditions. 
     
     
       4. The composition of  claim 1 , wherein the nanoparticle is a LDL or sLDL nanoparticle. 
     
     
       5. The composition of  claim 1 , wherein the ω-3 polyunsaturated fatty acid is docosahexaenoic acid (DHA). 
     
     
       6. The composition of  claim 1 , wherein the nanoparticle is a LDL or sLDL nanoparticle and further wherein the ω-3 polyunsaturated fatty acid is docosahexaenoic acid (DHA). 
     
     
       7. The composition of  claim 4 , wherein the LDL is human LDL. 
     
     
       8. The composition of  claim 5 , wherein DHA is incorporated into an LDL or sLDL nanoparticle. 
     
     
       9. The composition of  claim 4 , wherein ApoB100 is embedded in a phospholipid monolayer. 
     
     
       10. The composition of  claim 1 , wherein the composition is comprised in a pharmaceutically acceptable carrier. 
     
     
       11. A method for treating a subject having a cancer comprising administering an effective amount of a composition of  claim 1  to the subject. 
     
     
       12. The method of  claim 11 , wherein the cancer is a breast cancer, lung cancer, head and neck cancer, prostate cancer, esophageal cancer, tracheal cancer, brain cancer, liver cancer, bladder cancer, stomach cancer, pancreatic cancer, adrenal cancer, ovarian cancer, uterine cancer, cervical cancer, testicular cancer, colon cancer, rectal cancer, blood cancer, or skin cancer. 
     
     
       13. The method of  claim 12 , wherein the composition is administered systemically. 
     
     
       14. The method of  claim 12 , wherein the composition is administered intravenously, intradermally, intratumorally, intramuscularly, intraperitoneally, or subcutaneously, or by infusion local or regional to a tumor site. 
     
     
       15. The method of  claim 12 , further comprising administering at least a second anticancer therapy to the subject. 
     
     
       16. The method of  claim 15 , wherein the second anticancer therapy is a surgical therapy, chemotherapy, radiation therapy, cryotherapy, hormonal therapy, toxin therapy, immunotherapy or cytokine therapy. 
     
     
       17. The method of  claim 12 , wherein the subject is a human, or a non-human mammal. 
     
     
       18. The method of  claim 12 , wherein said cancer is metastatic, recurrent or multi-drug resistant. 
     
     
       19. The method of  claim 11 , wherein said composition is administered at least a second time.